This application, which during the past 2 1/2 years has been supported by an NSF grant, proposes to continue a series of studies initiated in 1981 to examine the hypothesis that the developing ovary, in addition to its hormonal regulation, is controlled by direct neural influences. We propose to analyze this issue by utilizing a combination of neuroendocrine, cell biology and molecular biology approaches, and have selected the following areas of inquiry: 1) To define, utilizing an immunological approach, the role of extrinsic noradrenergic nerves in the regulation of prepubertal ovarian function, 2) To pursue our recent findings that the immature ovary expresses the genes encoding nerve growth factor (NGF) and tyrosine hydroxylase (TH), the rate limiting enzyme in catecholamine biosynthesis, and test the hypothesis that NGF- supported cells of neural origin present in the ovary express the TH gene and produce norepinephrine (NE) independent of the presence of noradrenergic nerves 3) To examine the hypothesis that the content of ovarian vasoactive intestinal peptide (VIP) is directly controlled by the central nervous system independent of the anterior pituitary, and that VIP is an early neurogenic regulatory component of ovarian development able to initiate follicular formation and activate the gene expression of key steroidogenic enzymes before the immature ovary becomes subjected to gonadotropin control 4) To define the role of substance P (SP) and neuropeptide Y (NPY) as modulators of ovarian blood flow and 5) To examine the presence and functions of calcitonin-gene related peptide (CGRP) in the ovary.